115 research outputs found
Planet Populations as a Function of Stellar Properties
Exoplanets around different types of stars provide a window into the diverse
environments in which planets form. This chapter describes the observed
relations between exoplanet populations and stellar properties and how they
connect to planet formation in protoplanetary disks. Giant planets occur more
frequently around more metal-rich and more massive stars. These findings
support the core accretion theory of planet formation, in which the cores of
giant planets form more rapidly in more metal-rich and more massive
protoplanetary disks. Smaller planets, those with sizes roughly between Earth
and Neptune, exhibit different scaling relations with stellar properties. These
planets are found around stars with a wide range of metallicities and occur
more frequently around lower mass stars. This indicates that planet formation
takes place in a wide range of environments, yet it is not clear why planets
form more efficiently around low mass stars. Going forward, exoplanet surveys
targeting M dwarfs will characterize the exoplanet population around the lowest
mass stars. In combination with ongoing stellar characterization, this will
help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet
Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Description of two measles outbreaks in the Lazio Region, Italy (2006-2007). Importance of pockets of low vaccine coverage in sustaining the infection
<p>Abstract</p> <p>Background</p> <p>Despite the launch of the national plan for measles elimination, in Italy, immunization coverage remains suboptimal and outbreaks continue to occur. Two measles outbreaks, occurred in Lazio region during 2006-2007, were investigated to identify sources of infection, transmission routes, and assess operational implications for elimination of the disease.</p> <p>Methods</p> <p>Data were obtained from several sources, the routine infectious diseases surveillance system, field epidemiological investigations, and molecular genotyping of virus by the national reference laboratory.</p> <p>Results</p> <p>Overall 449 cases were reported, sustained by two different stereotypes overlapping for few months. Serotype D4 was likely imported from Romania by a Roma/Sinti family and subsequently spread to the rest of the population. Serotype B3 was responsible for the second outbreak which started in a secondary school. Pockets of low vaccine coverage individuals (Roma/Sinti communities, high school students) facilitated the reintroduction of serotypes not endemic in Italy and facilitated the measles infection to spread.</p> <p>Conclusions</p> <p>Communities with low vaccine coverage represent a more serious public health threat than do sporadic susceptible individuals. The successful elimination of measles will require additional efforts to immunize low vaccine coverage population groups, including hard-to-reach individuals, adolescents, and young adults. An enhanced surveillance systems, which includes viral genotyping to document chains of transmission, is an essential tool for evaluating strategy to control and eliminate measles</p
Accurate path integration in continuous attractor network models of grid cells
Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ~10â100 meters and ~1â10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other
Characterization of the Single Stranded DNA Binding Protein SsbB Encoded in the Gonoccocal Genetic Island
Background: Most strains of Neisseria gonorrhoeae carry a Gonococcal Genetic Island which encodes a type IV secretion system involved in the secretion of ssDNA. We characterize the GGI-encoded ssDNA binding protein, SsbB. Close homologs of SsbB are located within a conserved genetic cluster found in genetic islands of different proteobacteria. This cluster encodes DNA-processing enzymes such as the ParA and ParB partitioning proteins, the TopB topoisomerase, and four conserved hypothetical proteins. The SsbB homologs found in these clusters form a family separated from other ssDNA binding proteins. Methodology/Principal Findings: In contrast to most other SSBs, SsbB did not complement the Escherichia coli ssb deletion mutant. Purified SsbB forms a stable tetramer. Electrophoretic mobility shift assays and fluorescence titration assays, as well as atomic force microscopy demonstrate that SsbB binds ssDNA specifically with high affinity. SsbB binds single-stranded DNA with minimal binding frames for one or two SsbB tetramers of 15 and 70 nucleotides. The binding mode was independent of increasing Mg 2+ or NaCl concentrations. No role of SsbB in ssDNA secretion or DNA uptake could be identified, but SsbB strongly stimulated Topoisomerase I activity
Impact of bone-targeted therapies in chemotherapy-naĂŻve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302.
Background Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy.Objective Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naĂŻve mCRPC patients.Design, setting, and participants This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial.Intervention Patients were grouped by concomitant BTT use or no BTT use.Outcome measurements and statistical analysis Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models.Results and limitations While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients.Conclusions AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naĂŻve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT.Patient summary Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone.Trial registration ClinicalTrials.gov NCT00887198
A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma
In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity
The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication
Using their experiences from, and analysis of, global campaigns to eradicate smallpox, poliomyelitis, and measles, Myron Levine and colleagues derive lessons for malaria eradication
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